Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYDQ1QM)

• DOT Name: Lipid droplet assembly factor 1 (LDAF1)
• Synonyms: Promethin; Transmembrane protein 159
• Gene Name: LDAF1
• UniProt ID: LDAF1_HUMAN
• Pfam ID: PF16015
• Sequence:
  MAKEEPQSISRDLQELQKKLSLLIDSFQNNSKVVAFMKSPVGQYLDSHPFLAFTLLVFIV
  MSAVPVGFFLLIVVLTTLAALLGVIILEGLVISVGGFSLLCILCGLGFVSLAMSGMMIAS
  YVVVSSLISCWFSPRPLTQQNTSCDFLPAMKSAEFEGLYQE
• Function: Plays an important role in the formation of lipid droplets (LD) which are storage organelles at the center of lipid and energy homeostasis. In association with BSCL2/seipin, defines the sites of LD formation in the endoplasmic reticulum.
• Tissue Specificity: Expressed at high levels in the heart and skeletal muscle. Expressed at low levels in kidney, small intestine, lung and liver.

Molecular Interaction Atlas (MIA) of This DOT

9 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Lipid droplet assembly factor 1 (LDAF1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Lipid droplet assembly factor 1 (LDAF1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lipid droplet assembly factor 1 (LDAF1).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Lipid droplet assembly factor 1 (LDAF1).	[4]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lipid droplet assembly factor 1 (LDAF1).	[5]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Lipid droplet assembly factor 1 (LDAF1).	[6]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Lipid droplet assembly factor 1 (LDAF1).	[7]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Lipid droplet assembly factor 1 (LDAF1).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure affects the expression of Lipid droplet assembly factor 1 (LDAF1).	[10]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Lipid droplet assembly factor 1 (LDAF1).	[8]

References

• [1] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [5] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [6] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [7] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [8] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.